Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated potassium (Kv) and cyclic nucleotide-gated (CNG) channels. HCN channels contain the glycine-tyrosine-glycine (GYG) sequence that forms part of the selectivity filter, a similar structure than some potassium channels; however, they permeate both sodium and potassium, giving rise to an inward current. Yet a second amino acid sequence, leucine-cysteine-isoleucine (LCI), next to GYG, is well-preserved in all HCNs but not in the selective potassium channels. In this study we used site-directed mutagenesis and electrophysiology in frog oocytes to determine whether the LCI sequence affects the kinetics of HCN2 currents. Permeability and voltage dependence were evaluated, and we found a role of LCI in the gating mechanism combined with changes in ion permeability. The I residue resulted critical to this function.

超极化激活的环核苷酸门控（HCN）通道属于电压门控钾（Kv）和环核苷酸门控（CNG）通道的超家族。HCN通道包含形成选择性过滤器一部分的甘氨酸-酪氨酸-甘氨酸（GYG）序列，其结构与某些钾通道类似；但是，它们同时渗入钠和钾，从而产生内向电流。第二个氨基酸序列，亮氨酸-半胱氨酸-异亮氨酸（LCI），紧挨GYG，在所有HCN中都保存完好，但在选择性钾通道中没有保存。在这项研究中，我们使用了青蛙卵母细胞中的定点诱变和电生理学来确定LCI序列是否影响HCN2电流的动力学。评估了磁导率和电压依赖性，我们发现了LCI在门控机理与离子渗透率变化相结合中的作用。I残基导致对该功能至关重要。